Polygonatum Sibiricum Improved Cognitive Impairment Of Natural Aging Rats Through BDNF-TrkB Signaling Pathway

Background Currently,China has completely stepped into an aging society.Brain aging renders our bodies vulnerable to neurodegenerative diseases,which is the main cause of decreasing the living quality of elderly and their families.Objective This study aims to investigate the effect of polygonatum sibiricum（PS）on the cognitive decline of natural aging rats,and further explore the neuroprotective mechanism through BDNF-Trk B signaling pathway.Methods Thirty 17-month-old male Sprague-Dawley rats were randomly divided into aging model group,PS low-dose group and PS high-dose group.The aging model group was feeding with normal feed,PS low-dose and high-dose groups were administrated with PS at a dosage of 0.125 g·kg^-1and 0.5g·kg^-1via food,consistent for 5 months until 22-month-old.Another ten male rats aged 5 months were purchased as adult control group.Morris water maze test was conducted 7 days before the termination of the experiment to evaluate the effects of PS on spatial learning and memory.Then,the rats were sacrificed.The cerebral cortex and hippocampus tissue were collected and snap frozen for further study.Nissl staining was used to observe the changes of Nissl bodies in cortex and hippocampus.The morphology,ultrastructure of neurons and the number of synapses in cortex were observed by transmission electron microscopy.The protein expressions of PSD-95,synaptophysin,BDNF,p-Trk B and Trk B in cortex and hippocampus were evaluated by Western Blot.Results 1)The results of Morris water maze showed that the times of crossing the platform and the time of staying in the quadrant of the target platform were significantly decreased in aging rats,and PS effectively improved the cognitive function in natural aging rats.2)Nissl staining showed that compared with the adult group,the number of Nissl bodies decreased and the staining color became lighter in the cortex and hippocampus in aging group.After PS treatment,all the above changes significantly improved.3)The results of transmission electron microscope showed that compared with the adult rats,the number of lipofuscins increased,the intracytoplasmic organelles and the number of synapses significantly decreased in aging group.However,above pathological changes were remarkably improved after PS treatment.4)The results of Western Blot demonstrated that compared with the adult control group,the protein expression levels of PSD-95,synaptophysin,BDNF,p-Trk B/Trk B decreased in cortex and hippocampus in natural aging rats.And PS increases the expression of PSD-95,synaptophysin,BDNF and p-Trk B/Trk B.Conclusion PS can significantly ameliorate the cognitive dysfunction of natural aging rats.The underlying mechanism is that PS improves neurons function in hippocampus and cerebral cortex through regulating BDNF-Trk B signaling pathway,improves the morphology of neurons and enhances synaptic plasticity.